Venous thromboembolism (vte) is the third most common cardiovascular disease after mi and stroke

Venous thromboembolism (VTE) is the third most common cardiovascular disease after MI and stroke

• Venous thromboembolism (VTE) is the third most common cardiovascular disease after MI and stroke

• Current standard of treatment : heparin/vitamin K antagonist (VKA)

• New oral anticoagulants with and without heparin are effective and safe in the treatment of VTE

• Uncertainty exists about representation of more severe VTE in previous studies

Oral direct factor Xa inhibitor with a rapid onset of action and half-life of 10–14 hours

• Oral direct factor Xa inhibitor with a rapid onset of action and half-life of 10–14 hours

• 60 mg once daily dose was selected based on phase II data

• Dose of 30 mg in case of

• moderate renal impairment (CrCl 30 - 50mL/min)
• low body weight, i.e., ≤ 60 Kg
• concomitant use of P-gp inhibitors

Randomized, double blind, event driven, non-inferiority study

• Randomized, double blind, event driven, non-inferiority study

• Designed to broaden applicability to real world practice,

• by encouraging physicians to enroll all VTE patients

• Starting with standard parenteral heparin
• At least 3 months treatment, duration flexible
• All patients followed for 12 months
• Halving the dose for patients perceived to be at higher risk for bleeding

Efficacy

• Efficacy

• Primary : symptomatic recurrent VTE, i.e., the composite of DVT, non-fatal PE and fatal PE in the overall study period

• Secondary: symptomatic recurrent VTE , in the on-treatment period, in DVT and PE separately, and in severe PE with right ventricular dysfunction (NT-proBNP; spiral CT)

• Safety

• Principal : composite of major or clinically relevant non-major bleeding in the on-treatment period

• All outcomes were adjudicated by an independent clinical event committee

Hypothesis: LMW(Heparin)/edoxaban is non-inferior to LMW(Heparin)/warfarin for prevention of recurrent VTE

• Hypothesis: LMW(Heparin)/edoxaban is non-inferior to LMW(Heparin)/warfarin for prevention of recurrent VTE

• Estimated incidence of primary efficacy outcome with LMW(Heparin)/warfarin : 3% at 12 months

• Noninferiority margin of 1.5 for hazard ratio (corresponds to retention of at least 70 % of treatment effect of warfarin)

• Power 85%, two sided alpha of 0.05

• Sample size at least 7500

(LMW)heparin/edoxaban regimen

• (LMW)heparin/edoxaban regimen

• non-inferior to standard therapy for preventing recurrent VTE
• consistent efficacy in patients with DVT and PE
• clinically significant reduction in recurrent VTE in right ventricular dysfunction subgroup
• less clinically relevant bleeding
• constant effect over center TTR quartiles
• dose adaptation (30 mg) effective and safer

• Attractive regimen for full spectrum of VTE- patients

• DVT and PE separately

• PE with right ventricular dysfunction

• Relative efficacy over quartiles of center TTR

• Relative efficacy/safety in 30 mg dose group